Synthesis of the Isoxazole Ring

The synthetic routes to isoxazoles may be classified according to the number of isoxazole ring atoms in each component synthon (e.g., 3 + 2), 

Quilico, in Five- and Six-Membered Compounds with Oxygen and Nitrogen (R. H. Wiley, ed.), p. I. Wiley (Interscience), New York, 1962. 

Synthetic Routes Excluding Those Involving Chloroximes and Nitrile Oxides 

If one of the atoms of the CCC unit is part of an ester grouping, an isoxa-zolone will usually result if part of a cyano group, an aminoisoxazole will be formed. Substitution on the central atom of the CCC unit leads to 4-substitution in the resulting isoxazole. The NO unit is always hydroxylamine 

Reactions in which the CCC unit is part of a ring, with attack by hydroxyl-amine leading to a labile acyclic intermediate which recyclizes to form an isoxazole, are classified as ring transformations (Section II,B,4). 

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Of the possible methods of isoxazolidine ring formation (Scheme 1), the most important involves simultaneous formation of the 1 5 and 3 4 bonds (a). A limited number of reactions involve formation of the 1 5 and 2 3 bonds (b). This is also a standard synthesis of the isoxazole ring. 

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